SARS-CoV-2 spike protein mutations: Difference between revisions

In late December, 2020, there was news from '''South Africa''' of another lineage becoming prevalent there, termed '''501.V2'''<ref name="gisaid1">[https://www.gisaid.org/references/gisaid-in-the-news/novel-mutation-combination-in-spike-receptor-binding-site/ Novel variant 501.V2 with triple spike receptor binding site substit[utions] posted December 21, 2020 by the GSAID Influenza and Coronavirus sequences Initiative.</ref>, 501Y.V2, or '''B.1.351'''<ref name="cdc1">[https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html Emerging SARS-CoV-2 Variants], CDC report, update of January 3, 2021.</ref>.

In December, 2020, many scientists believed that B.1.1.7 is more contagious<ref name="nervtag1">[https://app.box.com/s/3lkcbxepqixkg4mv640dpvvg978ixjtf/file/756964987830 NERVTAG/SPI-M Extraordinary meetingon SARS-CoV-2 variant of concern 202012/01 (variant B.1.1.7)], December 21, 2020, from the UK Government [https://www.gov.uk/government/groups/new-and-emerging-respiratory-virus-threats-advisory-group New and Emerging Respiratory Virus Threats Advisory Group].</ref>, but there remained some uncertainty, since the increase in B.1.1.7 could also be related to founder effects or variations in human behaviors in regions of England<ref name="racaniello1">[https://www.virology.ws/2020/12/24/sars-cov-2-uk-variant-does-it-matter/ SARS-CoV-2 UK variant: Does it matter?], a 25 min video explanation recorded December 21, 2020, by Vincent Racaniello, Professor of virology at Columbia University, New York City.</ref>. However, by early January, 2021, it appeared very likely that B.1.1.7 and 501.V2 are more contagious<ref name="leonhardt1">[https://nyti.ms/2X7JT7z A simple chart shows why the new coronavirus variants are so worrisome], David Leonhardt, New York Times, January 4, 2021. A chart of new daily coronavirus cases shows Britain and South Africa surging, far exceeding rates in neighboring countries.</ref>.

Also in January, 2021, the lineage '''P.1''' was found to have increased rapidly in Manaus, Brazil<ref name="P1.1">[https://www.the-scientist.com/news-opinion/a-guide-to-emerging-sars-cov-2-variants-68387 A Guide to Emerging SARS-CoV-2 Variants] by Katarina Zimmer, ''The Scientist'', January 26, 2021.</ref><ref name="manaus1" />. P.1 has 10 mutations in the spike protein, including 3 in common with the South African lineage 501.V2 (N501Y, K417N, and E484K)<ref name="manaus1">[https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586 Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings], Nuno R. Faria ''et al.'' on behalf of the CADDE Genomic Networ,, January 12, 2021.</ref>. P.1 was found in the USA in January, 2021<ref name="P1.1" />.

These mutations also increase binding affinity for ACE2<ref name="zahradnik" />. Unlike B.1.1.7, 501.V2 retains His 69 and Val 70 (not deleted)<ref name="cdc1" />.

While the mutations in B.1.1.7 seem unlikely to make current anti-COVID-19 vaccines less effective, there is more concern regarding the additional mutations in 501.V2<ref name="smc1">[https://www.sciencemediacentre.org/expert-reaction-to-the-south-african-variant/ Expert reaction to the South African variant], Science Media Centre of the UK, January 4, 2021.</ref>. Unfortunately, poor management of COVID-19 and inconsistent therapy maneuvers have favored development of mutations that may evade the initial wave of vaccines<ref name="bieniasz">[https://www.virology.ws/2021/01/05/musings-of-an-anonymous-pissed-off-virologist/ Musings of an anonymous, pissed off virologist] by Paul Bieniasz, Professor at Rockefeller University, January 5, 2021.</ref>. Antibodies in the blood of half of people who have recovered from COVID-19 are unable to neutralize 501.V2<ref name="wibmer">[https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1 SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma], preprint posted January 19, 2021.</ref>, but other forms of immunity, such as T-cells, may still be protective. On January 28, 2021, Novavax reported that its vaccine, which was 90% effective in the UK, was '''only 50% effective in South Africa''', where ~90% of cases were 501.V2<ref name="novavax1">[https://ir.novavax.com/node/15506/pdf Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial], posted January 28, 2021 by Novavax.</ref>. The next day, Johnson and Johnson announced similar results<ref name="jnj1">[https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial#_ftn1 Johnson & Johnson Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial], January 29, 2021.</ref>. Experts believe that present vaccines could be modified for greater effectiveness against these mutants, if necessary, withinin a few months<ref name="smc1" />. Moderna began development of a vaccine modified to combat 501.V2 in January, 2021<ref name="moderna-501.v2">[https://www.businessinsider.com/moderna-to-test-coronavirus-vaccine-to-fight-south-africa-variant-2021-1 Moderna is designing a new version of its COVID-19 shot to fight the variant first found in South Africa] by  

*December 27, 2020: Added this section ''Update History''. Named and visualized the specific mutations of concern in the [[#501.V2|South African lineage 501.V2]], with a new citation<ref name="gisaid1" />.

*January 7, 2021: Added a preprint showing that some of the mutations in B.1.1.7 and 501.V2 increase binding affinity between the spike protein and its receptor ACE2<ref name="zahradnik" />.

*January 9, 2021: Added alternate name B.1.351 for 501.V2<ref name="cdc1" />.

*January 25, 2021: Convalescent plasma often ineffective against 501.V2<ref name="wibmer" /> and Moderna developing variant vaccine<ref name="moderna-501.v2" />.